From the Guidelines
A cardiac amyloidosis workup is warranted in patients with suspected heart failure who present with left ventricular wall thickness ≥14 mm in conjunction with fatigue, dyspnea, or edema, especially in the context of discordance between wall thickness on echocardiogram and QRS voltage on ECG. This recommendation is based on the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. The guideline suggests that patients with a high clinical suspicion for cardiac amyloidosis should undergo screening for serum and urine monoclonal light chains with serum and urine immunofixation electrophoresis and serum free light chains.
Key clinical features that suggest infiltrative cardiomyopathy and warrant a cardiac amyloidosis workup include:
- Unexplained left ventricular hypertrophy (especially with normal or low QRS voltage on ECG)
- Heart failure with preserved ejection fraction (HFpEF) resistant to standard therapies
- Unexplained right ventricular dysfunction
- Intolerance to standard heart failure medications, particularly ACE inhibitors and beta-blockers
- Conduction abnormalities without clear cause
- Additional red flags such as carpal tunnel syndrome, spinal stenosis, peripheral neuropathy, autonomic dysfunction, unexplained proteinuria, and a family history of amyloidosis
Certain populations deserve special consideration, including African Americans over 60 years old with unexplained heart failure or hypertrophy and men over 65 with HFpEF 1. Initial screening typically involves serum and urine protein electrophoresis, free light chain assay, ECG, echocardiography with strain imaging, and cardiac MRI if available. The 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis emphasizes the importance of a team-based approach to achieve optimal outcomes 1.
The ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis provide further guidance on diagnostic criteria and appropriate utilization 1. Early identification of cardiac amyloidosis is crucial, as new disease-modifying therapies have emerged, and timely diagnosis can significantly impact morbidity, mortality, and quality of life. Therefore, a cardiac amyloidosis workup should be initiated promptly in patients with suspected heart failure and clinical features suggestive of infiltrative cardiomyopathy.
From the Research
Indications for Cardiac Amyloidosis Workup
A cardiac amyloidosis workup is warranted in patients with suspected heart failure who exhibit certain clinical, imaging, and electrocardiographic clues that raise suspicion for cardiac amyloidosis 2. These clues include left ventricular wall thickening, heart failure, and arrhythmia with variable clinical presentation.
Patient Profiles
Patients who may benefit from a cardiac amyloidosis workup include:
- Those with heart failure with preserved ejection fraction (HFpEF) 3
- Individuals with worsening shortness of breath and signs of heart failure 4
- Patients with hypotension and reduced ejection fraction 4
- African-American patients, who may be at higher risk of being misdiagnosed with more common causes of heart failure 4
Diagnostic Approaches
The diagnostic workup for cardiac amyloidosis may involve:
- Echocardiography, which represents the first-line cardiac imaging modality for evaluation of heart failure and suspected cardiac amyloidosis 5, 6
- Serum protein electrophoresis with immunofixation of free light chain and urine protein electrophoresis 3
- Cardiac magnetic resonance 3
- Bone scintigraphy 3
Importance of Early Detection
Early detection of cardiac amyloidosis is crucial to prevent poor outcomes, as timely diagnosis and treatment can significantly improve survival 2, 4. Therefore, a high index of clinical suspicion is necessary to initiate a cardiac amyloidosis workup in patients with suspected heart failure.